Procedures for the combination of the A-chain with the B-chain of insulin will be developed for use in the synthesis of insulin from the two chains which are produced by biosynthesis in microorganisms. Mini-proinsulins will be produced semi-synthetically, from insulin and their conversion to insulin by chemical or enzymatic manipulations will be studied. Insulin derivatives which are modified at the carboxyl end of the B-chain (B23-30) will be prepared from desoctapeptide (B23-30) insulin hydrazide and their hormonal properties will be investigated to determine the relationship of structure to hormonal activity.